JP2010253372A - Gas-liquid stirrer - Google Patents
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- 239000007788 liquid Substances 0.000 title claims abstract description 36
- 238000003756 stirring Methods 0.000 claims abstract description 116
- 230000000630 rising effect Effects 0.000 claims 1
- 238000009792 diffusion process Methods 0.000 abstract 1
- 239000001963 growth medium Substances 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 238000004113 cell culture Methods 0.000 description 10
- 239000007789 gas Substances 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000002411 adverse Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005339 levitation Methods 0.000 description 1
- 239000010687 lubricating oil Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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- C12M27/02—Stirrer or mobile mixing elements
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Abstract
Description
本発明は、気液攪拌装置に関する。 The present invention relates to a gas-liquid stirring apparatus.
下記特許文献1には、培地が封入された培養槽の中央に上下2段の攪拌翼を備えると共に酸素の気泡を下部から攪拌槽内に噴出し、攪拌翼を回転させることによって酸素を培地中に溶け込ませる培養槽の運転制御装置が開示されている。
なお、下記特許文献2には、特許文献1のように酸素(気体)を培地(液体)中に溶け込ませるものではないが、液体を貯留する攪拌槽の内壁に垂直方向に延在する複数の邪魔板を備えると共に攪拌槽の中央に攪拌翼を備え、この攪拌翼を回転させることにより液体を攪拌させる攪拌装置が開示されている。
In the following Patent Document 1, an upper and lower two-stage stirring blade is provided at the center of a culture tank in which a culture medium is sealed, oxygen bubbles are blown into the stirring tank from below, and the stirring blade is rotated to allow oxygen to enter the culture medium. An operation control device for a culture tank to be dissolved in a cell is disclosed.
In Patent Document 2 below, oxygen (gas) is not dissolved in the culture medium (liquid) as in Patent Document 1, but a plurality of pieces extending in the vertical direction on the inner wall of the stirring tank storing the liquid are disclosed. There is disclosed a stirring device that includes a baffle plate and a stirring blade in the center of the stirring tank, and rotates the stirring blade to stir the liquid.
ところで、気体が液体に溶け込む量は、気泡の液体中における滞留時間が長くなる程多くなることが知られている。特許文献1の技術の場合、攪拌翼の回転による培地の下降流によって気泡は一端降下してから上昇する動きをとるが、気泡が培養槽の底に接触する程に攪拌翼の回転数を上げると、これ以上回転数を上げても滞留時間を上げることができない。すなわち、気泡の最大下降量は気泡の噴出し位置と培養槽の底との差によって物理的に規定されるので、気泡を下降させることによる滞留時間の拡大には限界がある。 By the way, it is known that the amount of gas dissolved in the liquid increases as the residence time of the bubbles in the liquid increases. In the case of the technique of Patent Document 1, the bubbles move upward after being lowered by the downward flow of the medium due to the rotation of the stirring blades, but the number of rotations of the stirring blades is increased so that the bubbles contact the bottom of the culture tank. Even if the number of rotations is further increased, the residence time cannot be increased. That is, since the maximum amount of bubbles to be lowered is physically defined by the difference between the bubble ejection position and the bottom of the culture tank, there is a limit to the extension of the residence time by lowering the bubbles.
本発明は、上述した事情に鑑みてなされたものであり、液体内における気泡の滞留時間を従来よりも長くすることにより、気体の液体への溶け込み量を増大させることを目的とするものである。 The present invention has been made in view of the above-described circumstances, and an object thereof is to increase the amount of gas dissolved in a liquid by making the residence time of bubbles in the liquid longer than before. .
上記目的を達成するために、本発明では、第1の解決手段として、液体を貯留する攪拌槽と、攪拌槽内に気泡を噴出する散気部と、攪拌槽内に垂下された駆動軸と、該駆動軸に多段に設けられた複数の攪拌翼と、を備え、各段の攪拌翼は、互いに異なる方向の力を液体に与える、という手段を採用する。 In order to achieve the above object, in the present invention, as a first solving means, a stirring tank for storing a liquid, an air diffuser for jetting bubbles into the stirring tank, and a drive shaft suspended in the stirring tank, And a plurality of stirring blades provided in multiple stages on the drive shaft, and the stirring blades at each stage employ a means that applies forces in different directions to the liquid.
第2の解決手段として、上記第1の解決手段において、攪拌翼は2段に設けられ、下段の攪拌翼は液体に下向きの力を与え、上段の攪拌翼は液体に上向きの力を与える、という手段を採用する。 As the second solution, in the first solution, the stirring blades are provided in two stages, the lower stirring blade gives a downward force to the liquid, and the upper stirring blade gives an upward force to the liquid. Adopt the means.
第3の解決手段として、上記第1または第2の解決手段において、各段の攪拌翼は、各方向に押し出された液体が上下方向における各段の攪拌翼の中間位置で衝突するように、所定の位相差θを持つ姿勢で駆動軸に取り付けられている、という手段を採用する。 As a third solution, in the first or second solution, the stirrer blades of each stage collide at a middle position of the stirrer blades of each stage in the vertical direction with the liquid pushed out in each direction. A means of being attached to the drive shaft in a posture having a predetermined phase difference θ is adopted.
第4の解決手段として、上記第1〜第3いずれかの解決手段において、散気部は、攪拌槽の下部に設けられる、という手段を採用する。 As a fourth solving means, in the first to third solving means, a means is adopted in which the air diffuser is provided in the lower part of the stirring tank.
第5の解決手段として、上記第1〜第4いずれかの解決手段において、攪拌槽の内壁において攪拌翼の間に位置する部位に設けられ、気泡の上昇を邪魔する邪魔板をさらに備える、という手段を採用する。 As a fifth solving means, in any one of the first to fourth solving means, it is further provided with a baffle plate which is provided at a position located between the stirring blades on the inner wall of the stirring tank and obstructs the rise of bubbles. Adopt means.
本発明によれば、各段の攪拌翼は、互いに異なる方向の力を液体に与えるので、上下方向に2つの液体の対流が発生する。そして、これら2つの対流によって気泡が運ばれるので、液体中における気泡の滞留時間を従来よりも長くすることが可能であり、この結果として気体の液体への溶け込み量を従来よりも増大させることができる。 According to the present invention, the stirrer blades at each stage apply forces in different directions to the liquid, so that convection of two liquids occurs in the vertical direction. Since the bubbles are carried by these two convections, the residence time of the bubbles in the liquid can be made longer than before, and as a result, the amount of gas dissolved in the liquid can be increased more than before. it can.
以下、図面を参照して、本発明の一実施形態について説明する。
図1及び図2に示すように、本実施形態に係る細胞培養装置Aは、培養槽1、駆動軸2、2つの攪拌翼3A、3B、下部軸受4A、上部軸受4B、連結器5、駆動モータ6、散気部7、4つの邪魔板8A〜8D及び伝熱ジャケット9から構成されている。詳細は後述するが、この細胞培養装置Aは、培養液Lを攪拌することにより酸素を培養液L中に溶け込ませて細胞を培養するものであり、気液攪拌装置の一種と考えることができる。
Hereinafter, an embodiment of the present invention will be described with reference to the drawings.
As shown in FIGS. 1 and 2, the cell culture apparatus A according to the present embodiment includes a culture tank 1, a drive shaft 2, two stirring blades 3A and 3B, a lower bearing 4A, an upper bearing 4B, a coupler 5, and a drive. The motor 6, the air diffuser 7, the four baffle plates 8 </ b> A to 8 </ b> D, and the heat transfer jacket 9 are configured. Although details will be described later, this cell culture device A is a device for culturing cells by dissolving the oxygen in the culture solution L by stirring the culture solution L, and can be considered as a kind of gas-liquid stirring device. .
培養槽1は、有底かつ円筒状の容器であり、図示するように中心軸線が鉛直方向となるように固定されている。このような培養槽1の内部には、所定量の培養液Lが貯留されている。この培養液Lは、培養対象となる細胞(より正確には粒子状の複数の細胞片)を含むと共に、当該細胞の栄養となる各種の栄養素を含む液体である。駆動軸2は、培養槽1の中心軸線に沿って上下方向に延在する棒状部材であり、途中部位の2箇所に攪拌翼3A、3Bが固定されている。また、この駆動軸2は、下端が下部軸受4Aを介して回転自在に培養槽1の底部に支持され、また上端が上部軸受4Bを介して回転自在に培養槽1の天井部に支持されている。 The culture tank 1 is a bottomed and cylindrical container, and is fixed so that the center axis is in the vertical direction as shown in the figure. A predetermined amount of the culture solution L is stored inside the culture tank 1. The culture solution L is a liquid that contains cells to be cultured (more precisely, a plurality of particulate cell pieces) and various nutrients that serve as nutrients for the cells. The drive shaft 2 is a rod-like member extending in the vertical direction along the central axis of the culture tank 1, and the stirring blades 3A and 3B are fixed at two locations in the middle. The lower end of the drive shaft 2 is rotatably supported by the bottom of the culture tank 1 via the lower bearing 4A, and the upper end of the drive shaft 2 is rotatably supported by the ceiling of the culture tank 1 via the upper bearing 4B. Yes.
2つの攪拌翼3A、3Bは、上述したように駆動軸2の途中部位の2箇所、つまり上下方向に延在する駆動軸2に上下2段に固定されている。これら2つの攪拌翼3A、3Bのうち、攪拌翼3Aは下段に設けられており、攪拌翼3Bは上段に設けられている。これら2つの攪拌翼3A、3Bは、図示するように、互いに直交する4つのパドルからなるパドル翼である。また、図1に示すように、下段に位置する攪拌翼3Aと上段に位置する攪拌翼3Bとは、各々のパドルの駆動軸2に対する傾きが逆向きになっている。すなわち、下段に位置する攪拌翼3Aの各パドルは駆動軸2に対して角度+αの傾きを有し、上段に位置する攪拌翼3Bの各パドルは駆動軸2に対して角度−αの傾きを有している。 As described above, the two stirring blades 3A and 3B are fixed in two upper and lower stages on the drive shaft 2 extending in the vertical direction at two locations in the middle of the drive shaft 2. Of these two stirring blades 3A and 3B, the stirring blade 3A is provided in the lower stage, and the stirring blade 3B is provided in the upper stage. These two stirring blades 3A and 3B are paddle blades composed of four paddles orthogonal to each other as shown in the figure. Further, as shown in FIG. 1, the lower stirrer blade 3A and the upper stirrer blade 3B have the inclinations of the respective paddles with respect to the drive shaft 2 reversed. That is, each paddle of the stirring blade 3A located at the lower stage has an inclination of an angle + α with respect to the drive shaft 2, and each paddle of the stirring blade 3B located at the upper stage has an inclination of an angle −α with respect to the driving shaft 2. Have.
このような2つの攪拌翼3A、3Bのうち、下段に位置する攪拌翼3Aは、駆動軸2周りに回転することにより培養槽1の下部に培養液Lの対流(矢印で示す下部対流RL)を発生させ、また上段に位置する攪拌翼3Bは、同じく駆動軸2周りに回転することにより培養槽1の上部に培養液Lの対流(矢印で示す上部対流RH)を発生させる。 Of these two stirring blades 3A and 3B, the lower stirring blade 3A rotates around the drive shaft 2 to cause convection of the culture medium L in the lower part of the culture tank 1 (lower convection R L indicated by an arrow). The stirring blade 3B located in the upper stage also rotates around the drive shaft 2 to generate convection of the culture medium L (upper convection R H indicated by an arrow) in the upper part of the culture tank 1.
また、これら2つの攪拌翼3A、3Bの位相差θは、図2に示すように、培養槽1の内側面近傍の各所(水平面内の各所)における下部対流RL及び上部対流RHの衝突高さHが各攪拌翼3A、3Bの中間位置近傍となるように最適設定されている。各攪拌翼3A、3Bは、何れも駆動軸2に固定されており、回転速度はお互いに同一なので、各攪拌翼3A、3Bによって発生する下部対流RL及び上部対流RHの流速は略同一と考えられる。 Further, as shown in FIG. 2, the phase difference θ between these two stirring blades 3A and 3B is a collision between the lower convection RL and the upper convection RH at various locations in the vicinity of the inner surface of the culture tank 1 (locations in the horizontal plane). The height H is optimally set so as to be in the vicinity of the intermediate position between the stirring blades 3A and 3B. Since each of the stirring blades 3A and 3B is fixed to the drive shaft 2 and has the same rotational speed, the flow rates of the lower convection RL and the upper convection RH generated by the stirring blades 3A and 3B are substantially the same. it is conceivable that.
したがって、培養槽1の内側面近傍における下部対流RL及び上部対流RHの衝突高さHは、下部対流RL及び上部対流RHの各流路長と位相差θとによって決定される。この両者のうち、下部対流RL及び上部対流RHの各流路長は、培養液Lの液面高さが一定で駆動軸2における各攪拌翼3A、3Bの取り付け位置が一定の場合には略一定と考えることができるので、攪拌翼3Aと攪拌翼3Bとの位相差θを調整することによって、下部対流RL及び上部対流RHの衝突高さHを培養槽1の内側面近傍の各所(水平面内の各所)において各攪拌翼3A、3Bの上下方向における位置の中間位置近傍に設定することができる。 Accordingly, the height H collision of the lower convection R L and an upper convection R H in the inner surface near the culture tank 1 is determined by the lower convection R L and an upper convection R each flow path length of the H and the phase difference theta. Among these, the flow path lengths of the lower convection RL and the upper convection RH are such that the liquid level height of the culture medium L is constant and the mounting positions of the stirring blades 3A and 3B on the drive shaft 2 are constant. Can be considered to be substantially constant, the collision height H of the lower convection RL and the upper convection RH is adjusted in the vicinity of the inner surface of the culture tank 1 by adjusting the phase difference θ between the stirring blade 3A and the stirring blade 3B. In each of these locations (each location in the horizontal plane), it can be set in the vicinity of an intermediate position in the vertical direction of each stirring blade 3A, 3B.
下部軸受4Aは、駆動軸2の下端を回転自在に培養槽1の底部に支持する。上部軸受4Bは、駆動軸2の上端を回転自在に培養槽1の天井部に支持する。これら下部軸受4A及び上部軸受4Bのうち、下部軸受4Aは、培養液Lに浸漬された状態で駆動軸2の下端部を回転自在に支持するもの、つまり培養液L中で軸受けとして機能するものなので、培養液L中に細胞の培養に悪影響を与えるような不要成分(潤滑油等)を放出しない構造のものが採用される。 The lower bearing 4A supports the lower end of the drive shaft 2 on the bottom of the culture tank 1 so as to be rotatable. The upper bearing 4 </ b> B supports the upper end of the drive shaft 2 on the ceiling of the culture tank 1 so as to be rotatable. Of these lower bearing 4A and upper bearing 4B, the lower bearing 4A is a member that rotatably supports the lower end of the drive shaft 2 while being immersed in the culture solution L, that is, a member that functions as a bearing in the culture solution L. Therefore, a structure that does not release unnecessary components (such as lubricating oil) that adversely affect cell culture in the culture solution L is employed.
連結器5は、駆動軸2の上端と駆動モータ6とを機械的に連結するものである。この連結器5は、例えば減速機能を有する減速器であり、駆動モータ6の回転を一定の減速比で駆動軸2に伝達する。駆動モータ6は、駆動軸2を回転駆動する動力源である。この駆動モータ6は、図示しない駆動回路から入力される駆動電流に基づいて駆動軸2を一定の回転速度で回転駆動する。 The coupler 5 mechanically connects the upper end of the drive shaft 2 and the drive motor 6. The coupler 5 is a speed reducer having a speed reducing function, for example, and transmits the rotation of the drive motor 6 to the drive shaft 2 at a constant speed reduction ratio. The drive motor 6 is a power source that rotationally drives the drive shaft 2. The drive motor 6 rotationally drives the drive shaft 2 at a constant rotational speed based on a drive current input from a drive circuit (not shown).
散気部7は、培養槽1の底部近傍に設けられ、酸素の気泡Gを培養槽1内(つまり培養液L中)に噴出する。この散気部7は、中空かつ多数の開口が表面に形成されたドーナツ状部材であり、外部の酸素供給源(図示略)から供給された酸素(O2)を各開口から培養液L中に噴射する。4つの邪魔板8A〜8Dは、培養槽1の内側面に垂直姿勢で等間隔に設けられた板状部材である。 The air diffuser 7 is provided in the vicinity of the bottom of the culture tank 1 and jets oxygen bubbles G into the culture tank 1 (that is, in the culture medium L). The air diffuser 7 is a donut-shaped member that is hollow and has a large number of openings formed on the surface thereof. Oxygen (O 2 ) supplied from an external oxygen supply source (not shown) is passed through each opening into the culture medium L. To spray. The four baffle plates 8 </ b> A to 8 </ b> D are plate-like members provided at equal intervals in a vertical posture on the inner surface of the culture tank 1.
すなわち、これら邪魔板8A〜8Dは、図2に示すように、駆動軸2を中心として互いに90°の角度に相当する培養槽1の内側面の4箇所に、垂直方向に延在するように設けられている。伝熱ジャケット9は、培養槽1の外周を覆うように設けられており、培養槽1を介して内部の培養液Lの温度を所定温度に維持するためのものである。 That is, as shown in FIG. 2, these baffle plates 8 </ b> A to 8 </ b> D extend vertically at four locations on the inner surface of the culture tank 1 corresponding to an angle of 90 ° with respect to the drive shaft 2. Is provided. The heat transfer jacket 9 is provided so as to cover the outer periphery of the culture tank 1, and is for maintaining the temperature of the culture medium L inside the culture tank 1 at a predetermined temperature.
次に、このように構成された細胞培養装置Aの作用効果について、図1を参照して詳しく説明する。 Next, the effect of the cell culture apparatus A configured as described above will be described in detail with reference to FIG.
本細胞培養装置Aの運転状態では、酸素供給源から散気部7に酸素が供給され、これによって散気部7の各開口から培養液Lに酸素の気泡Gが噴射される。一方、このような培養液L中への気泡Gの噴射と並行して、駆動モータ6が作動することによって鉛直方向に離間する2つの攪拌翼3A、3Bが培養液L中で回転運動を行う。 In the operating state of the cell culture apparatus A, oxygen is supplied from the oxygen supply source to the air diffuser 7, whereby oxygen bubbles G are jetted from the respective openings of the air diffuser 7 into the culture solution L. On the other hand, in parallel with the jetting of the bubbles G into the culture medium L, the two agitating blades 3A and 3B that are separated in the vertical direction by the operation of the drive motor 6 rotate in the culture medium L. .
そして、2つの攪拌翼3A、3Bのうち、下段に位置する攪拌翼3Aが回転運動を行うことによって、培養液Lは、図1に矢印で示すように、攪拌翼3Aの近傍において上から下に向けて対流し、培養槽1の内側面近傍において下から上に向けて対流する。一方、上段に位置する攪拌翼3Bが回転運動を行うことによって、培養液Lは、図1に矢印で示すように、攪拌翼3Bの近傍において下から上に向けて対流し、培養槽1の内側面近傍において上から下に向けて対流する。また、このような培養液Lの各対流は、各攪拌翼3A、3Bの回転によって発生するものなので、攪拌翼3A、3Bの回転方向の速度成分を含むものである。 Then, among the two stirring blades 3A and 3B, the stirring blade 3A located at the lower stage performs a rotational movement, so that the culture solution L is located in the vicinity of the stirring blade 3A from the top as shown by the arrow in FIG. The convection is performed in the vicinity of the inner surface of the culture tank 1 from the bottom to the top. On the other hand, when the stirring blade 3B located in the upper stage performs a rotational motion, the culture solution L convects from the bottom to the top in the vicinity of the stirring blade 3B as shown by an arrow in FIG. Convection from top to bottom near the inner surface. In addition, each convection of the culture solution L is generated by the rotation of the stirring blades 3A and 3B, and therefore includes a velocity component in the rotation direction of the stirring blades 3A and 3B.
そして、下段に位置する攪拌翼3Aの回転に起因する培養槽1の内側面近傍における下から上に向けた下部対流RLと上段に位置する攪拌翼3Bの回転に起因する培養槽1の内側面近傍における上から下に向けた下部対流RHとは、上下方向における2つの攪拌翼3A、3Bの位置の中間位置近傍で衝突する。 The lower convection RL directed from the bottom to the top in the vicinity of the inner surface of the culture tank 1 caused by the rotation of the stirring blade 3A located in the lower stage and the inside of the culture tank 1 caused by the rotation of the stirring blade 3B located in the upper stage The lower convection RH from the top to the bottom near the side surface collides in the vicinity of the middle position between the two stirring blades 3A and 3B in the vertical direction.
そして、この衝突によって、下段に位置する攪拌翼3Aの回転に起因する培養槽1の内側面近傍における下から上に向けた下部対流RLは、培養槽1の内側面近傍から培養槽1の中心方向(駆動軸2の方向)に向きを変える。そして、この攪拌翼3Aの回転に起因する下部対流RLは、攪拌翼3Aの上方に来ると、攪拌翼3Aの回転に起因する吸引力によって攪拌翼3Aの方向に向きを変え、攪拌翼3Aに向けて流れ込む。 Due to this collision, the lower convection RL from the bottom to the top in the vicinity of the inner surface of the culture tank 1 caused by the rotation of the stirring blade 3A located in the lower stage is caused to flow from the vicinity of the inner surface of the culture tank 1 to the culture tank 1. The direction is changed in the center direction (direction of the drive shaft 2). Then, when the lower convection RL caused by the rotation of the stirring blade 3A comes above the stirring blade 3A, the direction is changed in the direction of the stirring blade 3A by the suction force caused by the rotation of the stirring blade 3A. Flow towards the.
一方、上段に位置する攪拌翼3Bの回転に起因する培養槽1の内側面近傍における上から下に向けた上部対流RHは、培養槽1の内側面近傍から培養槽1の中心方向(駆動軸2の方向)に向きを変える。そして、この攪拌翼3Bの回転に起因する上部対流RHは、攪拌翼3Bの下方に来ると、攪拌翼3Bの回転に起因する吸引力によって攪拌翼3Bの方向に向きを変え、攪拌翼3Bに向けて流れ込む。 On the other hand, the upper convection RH from the upper side to the lower side in the vicinity of the inner surface of the culture tank 1 due to the rotation of the stirring blade 3B located in the upper stage is from the vicinity of the inner surface of the culture tank 1 to the center direction (drive) Change the direction to the direction of axis 2). Then, when the upper convection RH resulting from the rotation of the stirring blade 3B comes below the stirring blade 3B, the direction is changed to the direction of the stirring blade 3B by the suction force resulting from the rotation of the stirring blade 3B, and the stirring blade 3B Flow towards the.
すなわち、培養槽1内においては、培養液Lに上下2つの対流(下部対流RL及び上部対流RH)が発生し、これら下部対流RL及び上部対流RHは、互いに対流方向が逆向きである。下部対流RLは、攪拌翼3Aにおいて上から下に向かう流れであり、一方、上部対流RHは、攪拌翼3Bにおいて下から上に向かう流れである。 That is, in the culture tank 1, two upper and lower convections (lower convection RL and upper convection RH ) are generated in the culture medium L, and the lower convection RL and the upper convection RH are opposite to each other. It is. The lower convection RL is a flow from top to bottom in the stirring blade 3A, while the upper convection RH is a flow from bottom to top in the stirring blade 3B.
このような下部対流RL及び上部対流RHは、培養槽1の底部近傍の散気部7から噴射された多数の気泡Gに対して培養液Lの表面(上面)に容易に浮上させないように作用する。すなわち、散気部7から噴射された多数の気泡Gは、散気部7の上に位置する下段の攪拌翼3Aに起因する下部対流RLによって浮上に抗する力が作用し、容易に浮上することができない。 Such lower convection RL and upper convection RH do not easily float on the surface (upper surface) of the culture solution L with respect to a large number of bubbles G ejected from the air diffuser 7 near the bottom of the culture tank 1. Act on. That is, a large number of bubbles G ejected from the air diffuser 7 act as a force against the levitation due to the lower convection RL caused by the lower stirring blade 3A located above the air diffuser 7 and easily float. Can not do it.
また、気泡Gは、下部対流RLによって培養槽1の内側面近傍に運ばれるが、上段の攪拌翼3Bに起因する上部対流RHが下部対流RLに上方から衝突するので、培養槽1の内側面近傍においてそのまま浮上することはできず、下部対流RLによって培養槽1の中心方向に運ばれ、下段の攪拌翼3Aの吸引力によって当該攪拌翼3Aの下方に移動する。すなわち、散気部7から噴射された多数の気泡Gの殆どは、下部対流RLに沿って培養槽1の下部で巡回運動を行い、容易に浮上しない。 The bubble G is carried by the lower convection RL to the vicinity of the inner surface of the culture tank 1, but the upper convection RH caused by the upper stirring blade 3B collides with the lower convection RL from above, so that the culture tank 1 It cannot float as it is in the vicinity of the inner surface, but is carried toward the center of the culture tank 1 by the lower convection RL , and moves below the stirring blade 3A by the suction force of the lower stirring blade 3A. That is, most of the many bubbles G ejected from the air diffuser 7 perform a circular motion in the lower part of the culture tank 1 along the lower convection RL and do not easily float.
また、下部対流RLに沿って培養槽1の内側面近傍に運ばれた気泡Gの一部は、上部対流RHとの衝突の際に当該対流RH内に取り込まれる。しかしながら、上部対流RH内に取り込まれた気泡Gは、当該上部対流RHに沿って培養槽1の中心方向に運ばれるので、容易に浮上することができない。 Further, a part of the bubbles G carried along the lower convection RL to the vicinity of the inner surface of the culture tank 1 is taken into the convection RH when colliding with the upper convection RH . However, bubbles G taken into the upper convection R H is, since the conveyed toward the center of the culture tank 1 along the upper convection R H, not readily floated.
そして、上部対流RH内に取り込まれた気泡Gは、上段の攪拌翼3Bの吸引力によって当該攪拌翼3Bの上方に移動するが、上部対流RHの勢いが原因となってそのまま浮上するものは少なく、殆どが上部対流RHに沿って培養槽1の内側面近傍に移動して下降し、下部対流RLと衝突することによって上部対流RHに沿って培養槽1の上部で巡回運動を行い、容易に浮上しない。 The bubbles G taken into the upper convection RH move above the stirring blade 3B by the suction force of the upper stirring blade 3B, but rise as it is due to the momentum of the upper convection RH. Most of them are moved along the upper convection RH to the vicinity of the inner surface of the culture tank 1 and descend, and collide with the lower convection RL to make a circular motion in the upper part of the culture tank 1 along the upper convection RH. And does not surface easily.
さらに、下部対流RL及び上部対流RHは、攪拌翼3A、3Bの回転方向の速度成分を含むので、培養槽1の側部においては、各邪魔板8A〜8Dが障害物として作用することにより流れが乱される。 Furthermore, since the lower convection RL and the upper convection RH include velocity components in the rotational direction of the stirring blades 3A and 3B, the baffle plates 8A to 8D act as obstacles on the side of the culture tank 1. Disturbs the flow.
このような細胞培養装置Aによれば、培養槽1の底部近傍の散気部7から噴射された気泡Gは、その上方に上下2段に設けられた攪拌翼3A、3Bに起因する培養液Lの下部対流RL及び上部対流RHによって容易に浮上することができず、つまり培養液L中における滞留時間が従来よりも大幅に長くする。したがって、本細胞培養装置Aによれば、培養液L中への酸素の溶け込み量を従来よりも大幅に増大させることができる。 According to such a cell culture apparatus A, the bubbles G ejected from the air diffuser 7 near the bottom of the culture tank 1 are the culture solution caused by the stirring blades 3A and 3B provided above and below in two stages. The lower convection RL and the upper convection RH cannot easily float, that is, the residence time in the culture medium L is significantly longer than before. Therefore, according to the present cell culture apparatus A, the amount of oxygen dissolved in the culture medium L can be significantly increased as compared with the prior art.
また、下部対流RL及び上部対流RHが上下方向における各攪拌翼3A、3Bの中間位置で衝突するように、攪拌翼3Aと攪拌翼3Bとの位相差θが調整されているので、下部対流RLに沿って移動する気泡Gが上部対流RHに取り込まれる割合を小さくすることが可能であり、これによっても培養液L中における気泡Gの滞留時間を長くすることができる。 Further, since the phase difference θ between the stirring blade 3A and the stirring blade 3B is adjusted so that the lower convection RL and the upper convection RH collide with each other at an intermediate position between the stirring blades 3A and 3B in the vertical direction, It is possible to reduce the rate at which the bubbles G moving along the convection RL are taken into the upper convection RH , and this can also increase the residence time of the bubbles G in the culture solution L.
仮に、位相差θが最適設定されてなく、各攪拌翼3A、3Bの中間位置から大幅にズレた位置で下部対流RLと上部対流RHとが衝突した場合、例えば上下方向における攪拌翼3Aあるいは攪拌翼3Bの位置と同じような高さで下部対流RLと上部対流RHとが衝突した場合には、下部対流RLに沿って移動する気泡Gのうち上部対流RHに取り込まれる割合が多くなるので、気泡Gの滞留時間が比較的短い気泡Gの割合が増加する。 If the phase difference θ is not optimally set and the lower convection RL collides with the upper convection RH at a position significantly deviated from the intermediate position between the stirring blades 3A and 3B, for example, the stirring blade 3A in the vertical direction Alternatively, when the lower convection RL collides with the upper convection RH at the same height as the position of the stirring blade 3B, the bubbles G moving along the lower convection RL are taken into the upper convection RH. Since the ratio increases, the ratio of the bubbles G having a relatively short residence time increases.
また、下部対流RLに沿って移動する気泡Gの一部は邪魔板8A〜8Dの表面に沿って上昇するが、下部対流RLに対向する上部対流RHによって上昇が妨げられ、培養液Lの表面(上面)に容易に浮上することができない。 A part of the bubbles G moving along the lower convection RL rises along the surface of the baffle plates 8A to 8D, but the rise is hindered by the upper convection RH facing the lower convection RL , and the culture solution It cannot easily float on the surface (upper surface) of L.
なお、本発明は上記実施形態に限定されるものではなく、例えば以下のような変形例が考えられる。
(1)上記実施形態では、上下2段の攪拌翼3A、3Bを備える構成を採用したが、本発明はこれに限定されない。攪拌翼の段数(個数)はさらに多くても良い。
(2)上記実施形態では、各攪拌翼A、3Bとしてパドル翼を採用したが、本発明はこれに限定されない。細胞培養に供される攪拌翼には種々のものがあるので、それら各種の翼を攪拌翼として用いても良い。
In addition, this invention is not limited to the said embodiment, For example, the following modifications can be considered.
(1) In the embodiment described above, the configuration including the upper and lower two-stage stirring blades 3A and 3B is adopted, but the present invention is not limited to this. The number of stirring blades (number) may be larger.
(2) In the above embodiment, paddle blades are employed as the stirring blades A and 3B, but the present invention is not limited to this. Since there are various types of stirring blades used for cell culture, these various blades may be used as the stirring blades.
(3)上記実施形態では、2つの攪拌翼3A、3Bの種類(形状)や回転数を全く同一としたが、本発明はこれに限定されない。
(4)上記実施形態では4つの邪魔板8A〜8Dを設ける構成を採用したが、本発明はこれに限定されない。本発明では、多段に設けられた攪拌翼が邪魔板8A〜8Dの機能をも奏するので、邪魔板8A〜8Dを削除または個数を削減しても良い。
(3) In the above embodiment, the types (shapes) and rotation speeds of the two stirring blades 3A and 3B are exactly the same, but the present invention is not limited to this.
(4) In the above embodiment, the configuration in which the four baffle plates 8A to 8D are provided is adopted, but the present invention is not limited to this. In the present invention, the stirring blades provided in multiple stages also function as the baffle plates 8A to 8D. Therefore, the baffle plates 8A to 8D may be deleted or the number thereof may be reduced.
(5)上記実施形態では、攪拌翼3Aと攪拌翼3Bとの位相差θを調整することにより、下部対流RL及び上部対流RHの衝突高さHを攪拌翼3Aと攪拌翼3Bとの中間位置に設定したが、本発明はこれに限定されない。下部対流RLの流路長と上部対流RHの流路長との差を調整することによって攪拌翼3Aと攪拌翼3Bとの中間位置で下部対流RL及び上部対流RHが衝突するようにしても良い。 (5) In the above embodiment, the collision height H of the lower convection RL and the upper convection RH is adjusted between the stirring wing 3A and the stirring wing 3B by adjusting the phase difference θ between the stirring wing 3A and the stirring wing 3B. Although the intermediate position is set, the present invention is not limited to this. By adjusting the difference between the flow path length of the lower convection RL and the flow path length of the upper convection RH , the lower convection RL and the upper convection RH collide at an intermediate position between the stirring blade 3A and the stirring blade 3B. Anyway.
A…細胞培養装置、1…培養槽、2…駆動軸、3A、3B…攪拌翼、4A…下部軸受、4B…上部軸受、5…連結器、6…駆動モータ、7…散気部、8A〜8D…邪魔板、9…伝熱ジャケット、L…培養液、G…気泡(酸素) DESCRIPTION OF SYMBOLS A ... Cell culture apparatus, 1 ... Culture tank, 2 ... Drive shaft, 3A, 3B ... Stirrer blade, 4A ... Lower bearing, 4B ... Upper bearing, 5 ... Coupler, 6 ... Drive motor, 7 ... Air diffuser, 8A ~ 8D ... baffle plate, 9 ... heat transfer jacket, L ... culture solution, G ... bubbles (oxygen)
Claims (5)
前記攪拌槽内に気泡を噴出する散気部と、
前記攪拌槽内に垂下された駆動軸と、
該駆動軸に多段に設けられた複数の攪拌翼と、を備え、
各段の攪拌翼は、互いに異なる方向の力を液体に与えることを特徴とする気液攪拌装置。 A stirring tank for storing liquid;
An air diffuser for ejecting bubbles into the stirring tank;
A drive shaft suspended in the stirring vessel;
A plurality of stirring blades provided in multiple stages on the drive shaft,
A gas-liquid stirring apparatus, wherein the stirring blades at each stage apply forces in different directions to the liquid.
The gas-liquid according to any one of claims 1 to 4, further comprising a baffle plate that is provided at a position located between the stirring blades on the inner wall of the stirring tank and prevents the bubbles from rising. Stirring device.
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